Fluticasone propionate synthesis
- Product Name:Fluticasone propionate
- CAS Number:80474-14-2
- Molecular formula:C25H31F3O5S
- Molecular Weight:500.57
Fluticasone propionate can be synthesized from 9 by using BrCH2F,2a ClCH2F,5a or S-(monofluoromethyl) diarylsulfonium tetrafluoroborate 5f,g directly. Using BrCH2F can get an ideal yield; however, BrCH2F is costly and will destroy to the ozone layer. In addition, 9 reacted with BrCH2Cl or Br2CH2 and then by an anion exchange with AgF,2c,5e KF, or tetrabutylammonium fluoride5b to afford 1 in a low yield.
Improved Synthesis of Fluticasone Propionate
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Yield:80474-14-2 91.7%
Reaction Conditions:
with potassium hydrogencarbonate in N,N-dimethyl-formamide at -10 - 20; for 2 h;
Steps:
1-11 Substitution into ester reaction:
In a four-necked bottle, add 31.7g IM4 and 159ml dimethylformamide, lower the temperature to below 20 , add 7.2g potassium bicarbonate,Then lower the temperature to below -10 ,Add 8.7g of fluorobromomethane dropwise,Then control the temperature -10-20 for 2 hours, after the IM4 reaction is detected by HPLC, add 1mol / L hydrochloric acid dropwise, adjust the PH value to 2, crystallize, filter, wash and dry to obtain 32.5g crude fluticasone propionate, this step The molar yield is 96.3%.Refining reaction: In a four-necked bottle, add 31.2g crude fluticasone propionate and 437ml acetone, raise the temperature to 55 , stir to dissolve, control the temperature 50-60 , add 250ml of purified water dropwise, then slowly lower the temperature Crystallization below 15 , filtration, washing and drying to obtain 28.6g crude fluticasone propionate, the molar yield of this step is 91.7%.
References:
CN110698530,2020,A Location in patent:Page/Page column 7-15
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